June 2026 Research Update

This month added a clearer, more practical picture of how breathing and pregnancy can intersect with Pompe disease care. Across these studies, enzyme replacement therapy (ERT) during pregnancy did not show infusion reactions or reported harmful outcomes for mothers or babies, while breathing support (noninvasive ventilation) was linked to rapid improvement when breathing problems were present. Together, they emphasize that respiratory changes can be important in day-to-day function and can shift over time, especially during major life periods like pregnancy. [1] [2] [3]

In a French and Dutch multicenter review of 14 pregnancies in 11 women, some women continued ERT (alglucosidase alfa or avalglucosidase alfa) during pregnancy and others paused it early, but no infusion-associated reactions were reported during pregnancy or after restarting. Many pregnancies with available clinical tracking showed a mild decline in walking distance or breathing test results during pregnancy, and most people with follow-up data recovered to pre-pregnancy levels within 1 to 2 years after delivery. The study also noted that some deliveries were planned with maternal safety in mind. [1]

Respiratory support also appeared important in both children and adults, although the evidence is from small datasets. In 22 French children in the ERT era, sleep studies showed that many had largely preserved nighttime breathing, but some had obstructive sleep apnea and a smaller number had high carbon dioxide levels, with several children starting, continuing, or weaning off noninvasive ventilation over time. In a single adult case with pulmonary hypertension and respiratory failure, noninvasive ventilation was followed by rapid improvement in blood gases and later normalization of estimated pulmonary artery pressure on heart ultrasound. [2] [3]

For patients and caregivers, these studies mainly add real-world context rather than proving what will happen for any one person. The pregnancy report offers cautious reassurance that, in this small group, continuing ERT during pregnancy was not linked to infusion reactions or reported harms for mother or child, while also showing that temporary changes in walking ability or breathing measures can occur and may improve after pregnancy. The sleep and adult respiratory case reports underline that breathing problems in Pompe disease can show up as sleep-related breathing issues or daytime respiratory failure, and that noninvasive ventilation can be part of how these problems are managed, with needs sometimes changing over time. Important uncertainties remain because the pregnancy and sleep data were limited in size and the adult respiratory finding comes from one person. [1] [2] [3]

This month strengthened two parts of the diagnosis and monitoring story: avoiding false alarms on screening tests, and measuring muscle involvement more precisely. One genetic study showed that a specific GAA gene haplotype can cause low dried blood spot enzyme activity without causing symptoms unless combined with additional disease-causing variants. Imaging studies also showed that quantitative muscle imaging can pick up distinct muscle patterns by age/phenotype and that fat replacement in muscle can increase over time and relate to changes in function. [4] [5] [6]

In a Chinese high-risk screening program (22 people from 11 families), the GAA c.[752C>T;761C>T] haplotype was linked to low dried blood spot GAA activity even when people had no Pompe disease symptoms. Pompe disease features were reported only when this haplotype was paired (in trans) with two pathogenic variants, while people with the haplotype alone or with only one pathogenic variant remained asymptomatic. The study described this as a pseudodeficiency allele, meaning a genetic pattern that can look abnormal on enzyme screening but does not necessarily mean disease. [4]

Two muscle imaging studies suggested that fat fraction (a measure of fat replacement in muscle) may be a particularly useful way to track progression in late-onset Pompe disease, while water T2 (a measure that can reflect muscle changes beyond fat) may add extra information. In an adult 2-year follow-up study of 8 late-onset patients on ERT compared with 8 controls, fat fraction rose over time in several thigh muscle groups and was linked to worsening clinical scores, while other imaging measures were mostly stable over time. In a separate cross-sectional study including classic infantile and young late-onset patients, imaging showed different patterns by group, with more lower-leg involvement in infantile cases and more thigh (especially adductor) involvement in late-onset cases, and more extensive thigh involvement related to lower motor function scores. [5] [6]

For patients, these studies speak to two common concerns: getting the diagnosis right and measuring change in a way that matches lived experience. The genetic screening report helps clarify why someone can have a low enzyme screening result but not have symptoms, especially in East Asian populations where this haplotype was enriched, and why follow-up genetic testing can be important for interpretation. The imaging studies suggest that muscle imaging can sometimes show involvement even when changes are subtle, and that increasing muscle fat replacement can track with functional changes over time, although the long-term study was small and needs confirmation in larger groups. These findings may matter more for understanding test results and research tracking than for immediate day-to-day decisions. [4] [5] [6]

This month included early laboratory research and several case reports that do not predict what will happen for most people, but they expand the map of what can occur. The lab study tested a strategy to help enzyme replacement therapy work better inside cells, and it reported improved processing and activity of the replacement enzyme in patient-derived fibroblasts. The case reports showed that Pompe disease can present in unexpected ways (like long-standing abnormal liver enzymes from muscle rather than liver disease), and that infections related to catheters or severe viral illness can be major events in some individuals. [7] [8] [9] [10]

In a laboratory study using fibroblasts from three Pompe disease cell lines, two TRPML1 agonists (WR54-006 and WR7-003) increased the availability of a key receptor involved in bringing enzyme into cells and improved the processing and lysosomal delivery of rhGAA when the replacement enzyme was present. When combined with rhGAA, the study reported higher GAA activity in cells, and this effect was blocked by a TRPML1 inhibitor, supporting that the change was linked to TRPML1 activation. This is proof-of-concept work in cells, so it mainly shows what might be possible rather than what will work in people. [7]

Across case reports, the shared message was variability in presentation and risk that depends heavily on individual circumstances. One report described an infant with infantile-onset Pompe disease receiving weekly ERT through a central venous catheter who developed a bloodstream infection that cleared with targeted antibiotics without removing the catheter, while standard blood culture was important when rapid molecular tests were negative. Another report described a child with late-onset Pompe disease who developed a severe disseminated adenovirus infection with an HLH-like illness, with deep sequencing showing different viral populations across body compartments during the course. A separate case described an athletic 18-year-old with persistently elevated AST, ALT, and CK who ultimately was diagnosed with late-onset Pompe disease after liver testing was unrevealing, and her twin sister carried the same variants and low enzyme activity. [9] [10] [8]

For patients and caregivers, this section is mainly about understanding possibilities rather than drawing general rules. The cell study is early research that may matter later if it leads to treatments that improve how well replacement enzyme reaches muscles, but it has not been tested in animals or people in these summaries. The case reports are individual stories: they can help explain why a person might be evaluated for liver disease when the main issue is muscle, and they show that device-related infections or severe viral infections can occur in specific contexts. What remains uncertain is how often these situations happen in the broader Pompe population and which factors most strongly predict them, because case reports cannot answer those questions. [7] [9] [10] [8]